A Phase Ib/II Trial of Lenvatinib Plus Pembrolizumab Plus Fulvestrant in ER-positive/ HER2- Negative Metastatic Breast Cancer

Plain English Summary

A Study of Lenvatinib, Pembrolizumab, and Fulvestrant in People With Breast Cancer is a Phase 2 clinical trial sponsored by Memorial Sloan Kettering Cancer Center studying Metastatic Breast Cancer. This trial is testing a combination of three drugs: lenvatinib, pembrolizumab, and fulvestrant. It is for patients with ER-positive, HER2-negative metastatic breast cancer that has spread and has not responded well to previous treatments. Participants will receive the combination therapy, and their health will be closely monitored. Standard chemotherapy or other approved treatments for this type of breast cancer are existing alternatives. The trial aims to enroll 49 participants.

Official Summary

The purpose of this study is to test whether the combination of lenvatinib, pembrolizumab, and fulvestrant is a safe and effective treatment that causes few or mild side effects in people with ER+/HER2- metastatic breast cancer.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients must be 18 years or older with a confirmed diagnosis of advanced or metastatic ER+/HER2- breast cancer. Patients should have received at least one prior endocrine therapy combined with a CDK 4/6 inhibitor. Patients with stable brain metastases that are not progressing may be eligible. Individuals with a life expectancy of at least 12 weeks and good overall health (ECOG performance status 0-1) are needed. This trial is studying Metastatic Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures the safety of the drug combination and helps determine the right dose for future studies, meaning it focuses on how well patients tolerate the treatment and what side effe The specific primary outcome measures are: The number of adverse events and dose-limiting toxicities to find the Recommended Phase 2 Dose (RP2D) (1 year). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to find a new treatment option for patients with ER+/HER2- metastatic breast cancer who have limited treatment choices after standard therapies have failed. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Metastatic Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a significant patient population with limited treatment options, suggesting a potential market for effective new therapies in metastatic breast cancer. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for you, considering your specific cancer type and treatment history. Be prepared for regular clinic visits for drug administration, blood tests, and scans to monitor your health and the cancer's response. You will need to commit to using effective birth control if you are of childbearing potential, and men must also use contraception. This trial is currently recruiting participants. The trial is being conducted at 7 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 49 participants

Interventions

• DRUG: Lenvatinib — 20mg orally PO daily
• DRUG: Pembrolizuma — 400mg IV Q6W
• DRUG: Fulvestrant — 500mg IM Q4W

Primary Outcomes

• The number of adverse events and dose-limiting toxicities to find the Recommended Phase 2 Dose (RP2D) (1 year)

Secondary Outcomes

• Overall response rate (ORR) (24 weeks)

Full Eligibility Criteria

Inclusion Criteria:

* Male or female participants who are ≥18 years old with histologically confirmed diagnosis of unresectable locally advanced or MBC.
* Male participants or premenopausal females are eligible as long as they are on LHRH agonist for at least four weeks prior to starting trial therapy and commit to continue LHRH agonist for as long as patient is receiving trial therapy or medical contraindications arise
* Patients diagnosed with ER+ (ER \>1%), HER2- breast cancer as per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
* Progressed on at least 1 prior endocrine therapy combined with CDK 4/6 inhibitor. Prior fulvestrant therapy is permitted.
* Have not received more than 2 lines of chemotherapy in the metastatic setting.
* Stable previously treated brain metastases i.e. without radiological evidence of progression for at least 4 weeks (note that repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at
* Life expectancy of ≥12 weeks.
* A newly obtained biopsy of non-irradiated tumor must be available prior to the first dose of study drug for biomarker analysis. Patients with inaccessible tumors for biopsy specimens can be enrolled without a biopsy (if archival tissue is available within the previous 6-12 months) upon consultation and agreement by the Principal Investigator. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are favored over slides and fresh tissue biopsies are preferred over archival tissue
* The participant provides written informed consent for the trial.
* Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
* Have adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no change in antihypertensive medications within 1 week prior to randomization.
* Have adequate organ function. Specimens must be collected within 14 days prior to the start of study intervention.
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
* Is not a woman of childbearing potential (WOCBP) OR
* Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab or 30 days post lenvatinib, whichever occurs last.

The investigator should evaluate the potential for contraceptive method failure (i.e.,noncompliance, recently initiated) in relationship to the first dose of study intervention

* A WOCBP must have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin \[β-hCG\]) within 72 hours before the first dose of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
* Additional requirements for pregnancy testing during and after study intervention.
* The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
* Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of lenvatinib:
* Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
* Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below:
* Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.

Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penilevaginal penetration.

Please note that 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed.

Criteria for known Hepatitis B and C positive subjects:

* Hepatitis B and C screening tests are required as per MSK policy but do not need to be repeated prior to study unless there is a known history of Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection.
* Participants who have active hepatitis B infection (defined as HBsAg positive and/or detectable

Trial Locations

• Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities), Basking Ridge, New Jersey, United States
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities), Middletown, New Jersey, United States
• Memorial Sloan Kettering Bergen (Limited Protocol Activities), Montvale, New Jersey, United States
• Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities), Commack, New York, United States
• Memorial Sloan Kettering Westchester (Limited Protocol Activities), Harrison, New York, United States
• Memorial Sloan Kettering Cancer Center (All Protocol Activities), New York, New York, United States
• Memorial Sloan Kettering Nassau (Limited Protocol Activities), Uniondale, New York, United States

Frequently Asked Questions

Related Conditions

• Metastatic Breast Cancer
• ER-positive Breast Cancer
• HER2-negative Breast Cancer
• Hormone Receptor-positive Breast Cancer
• Endocrine Therapy Resistance
• CDK 4/6 Inhibitor Resistance
• Advanced Breast Cancer
• Metastatic Cancer
• Oncology
• Cancer Treatment

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